Liposomes

Abstract

Liposomes with covalently bound PEG moieties on the external surface which demonstrate improved serum half-life following intravenous administration are provided.

What is claimed is: 
     
       1. Liposomes having PEG moieties covalently bound to phospholipids on the external surface, wherein said liposomes are selected from large unilamellar vesicles (LUV's), small unilamellar vesicles (SUV's) and multilamellar vesicles (MLV's). 
     
     
       2. Liposomes according to claim 1, wherein said liposomes comprise a mixture of lipids. 
     
     
       3. Liposomes according to claim 2 wherein the lipid bilayers comprise a 7:3 to 5:5 molar ratio of DOPC to DOPE. 
     
     
       4. Liposomes according to claim 2 wherein the lipid bilayers comprise a mixture of dioleylphosphatidylcholine (DOPC) and dioleylphosphatidylethanolamine (DOPE). 
     
     
       5. A pharmaceutical composition comprising an aqueous suspension of liposomes according to claim 1 and a pharmaceutically acceptable carrier or diluent. 
     
     
       6. A process for producing a liposome according to claim 1 comprising treating liposomes with a polyethylene glycol having at least one activating group capable of coupling said polyethylene glycol to said liposome. 
     
     
       7. A process according to claim 6 wherein the reactive derivatave is 2,2,2-trifluoroethane sulphonyl-monomethoxy-polyethylene glycol. 
     
     
       8. Liposomes according to claim 1, obtained by reacting 2,2,2-trifluoroethane sulfonyl-monomethoxy PEG derivatives with liposomes. 
     
     
       9. Liposomes according to claim 1, wherein essentially all said PEG moieties are bound on the external surface of the liposome. 
     
     
       10. Liposomes according to claim 1, wherein said liposomes display an enhanced partition to the PEG-rich (upper) phase of a PEG:dextran aqueous two phase system in which liposomes not having PEG moieties covalently bound to phospholipids on the external surface separate predominantly to the interface or bottom phase. 
     
     
       11. Liposomes according to claim 1, wherein said liposomes display a decreased adsorption of serum proteins than liposomes not having PEG moities covalently bound to phospholipids on the external surface.